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Does lymphopenia or macrocytosis reflect 6‐thioguanine levels in patients with inflammatory bowel disease treated with azathioprine or 6‐mercaptopurine?
Author(s) -
Heerasing N. M.,
Ng J. F.,
Dowling D.
Publication year - 2016
Publication title -
internal medicine journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.596
H-Index - 70
eISSN - 1445-5994
pISSN - 1444-0903
DOI - 10.1111/imj.12915
Subject(s) - medicine , thiopurine methyltransferase , mercaptopurine , gastroenterology , inflammatory bowel disease , mean corpuscular volume , azathioprine , macrocytosis , lymphocyte , immunology , rank correlation , disease , hematocrit , anemia , machine learning , computer science
Background The thiopurine drugs, 6‐mercaptopurine and azathioprine, remain the mainstay of immunomodulator therapy for inflammatory bowel disease (IBD). Optimal management depends on achieving therapeutic levels of 6‐thioguanine (6‐TGN), but measuring thiopurine metabolites is associated with significant cost. Thiopurines cause lymphopenia and an increase in mean corpuscular volume (MCV). It is unclear whether any clinically useful correlation exists between 6‐TGN levels and lymphocyte count or MCV. Aims The aim of this study is to investigate the correlation between 6‐TGN levels and lymphocyte count and MCV in thiopurine‐treated patients with IBD. Methods We analysed a prospectively acquired database of 67 patients with IBD treated with thiopurine therapy. The data were analysed looking at the relationship between 6‐TGN levels and both lymphocyte count and MCV by using the Spearman's rank correlation coefficient. Results Twenty‐seven (40%) patients had therapeutic 6‐TGN levels. Thirty‐three (49%) patients had sub‐therapeutic 6‐TGN levels. A weak positive correlation between 6‐TGN levels and lymphocyte count was demonstrated, but this was not statistically significant (Spearman's R = 0.14, P = 0.23). Spearman's rank correlation coefficient between 6‐TGN levels and MCV was statistically significant ( R = 0.42, P = 0.0005). MCV >101 fL excluded a subtherapeutic 6‐TGN level with positive predictive value of 92%. Conclusions There is no specific lymphopenia that can be assumed to indicate a therapeutic 6‐TGN level. The relationship between 6‐TGN levels and MCV is likely to be clinically relevant. If MCV is elevated, 6‐TGN is unlikely to be sub‐therapeutic. MCV is a potential surrogate marker which can rule out sub‐therapeutic thiopurine metabolites in patients with IBD treated with azathioprine or 6‐mercaptopurine.